(a) Technical Field
The present invention relates to temperature-sensitive nano-carriers.
(b) Background Art
Nanoparticle systems for delivering therapeutic proteins or drugs are generally synthesized by emulsion evaporation using organic solvents. However, these conventional methods need to include complicated steps, and also have problems associated with the use of organic solvents such as cytotoxicity and an increasing preparation cost (T. G. Park, et al., Biomacromolecules 8 (2007) 650-656; T. G. Park, et al., Biomacromolecules 7 (2006) 1864-1870; D. T. Birnbaum, et al., J. Control. Rel. 65 (2000) 375-387). For these reasons, there have been extensive researches exerted to develop a novel method of preparing nanoparticles that can ensure the stability of drugs encapsulated inside nanoparticles.
To overcome these problems, there have been attempts to use supercritical fluids, which are nontoxic solvents, for the preparation of nanoparticles. However, this process is not widely employed because most polymers exhibit a limited solubility in supercritical fluids (K. S. Soppimath et al., J. Control. Rel. 70 (2001) 1-20).
U.S. Pat. No. 5,019,400 discloses a process of preparing microspheres for protein drug delivery by spraying a biocompatible polymer, poly(D,L-lactic acid-co-glycolic acid) (referred to as ‘PLGA’ hereinafter), into cold liquid. However, organic solvent was used for dissolving PLGA, and the hydrophobicity of the organic solvent used for dissolving PLGA causes various problems.
U.S. Pat. No. 6,586,011 discloses a process of preparing a nanoparticle system for protein delivery by means of spraying into a cold liquid. However, a crosslinking agent used for manufacturing nanoparticles seriously damages the stability of the protein drugs.
A solvent evaporation method used for preparing nanoparticles also generates various problems associated with the use of organic solvent. Meanwhile, a salting-out method has been developed as an attempt to use a water-miscible organic solvent (e.g., acetone) instead of highly hydrophobic and toxic organic solvent for preparing poly(D,L-lactic acid) (referred to as ‘PLA’ hereinafter) nanoparticles (E. et al., Pharm. Res. 10 (1993) 1732-1737). However, this method still has problems such as a lowered activity and stability of protein drugs.
The information disclosed in the above Background section is only for the enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.
All publications, patents and patent applications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference.